Transdermal drug delivery and monitoring systems are desirable in many circumstances in that self-administration by untrained persons is required. For example, transdermal drug patches are available commercially for curbing nicotine cravings due to smoking, as a birth-control aid, for pain relief, and a wide variety of specific applications. A principal benefit of transdermal drug delivery as compared to the historical use of injectable dosage forms is that it provides the drug directly to the blood stream without the discomfort of needles, lancets and other sharp instruments, and without the need for training in the use and disposal of such instruments. As compared to oral dosage forms, transdermal delivery can be more effective for some regimens when it is desirable to deliver a drug clear of the hostile environment presented by gastrointestinal juices or by first pass metabolism. Further, transdermal devices permit monitoring of blood components.
A popular form for transdermal drug delivery systems is a patch having an adhesive layer or perimeter suitable for adhering the patch to skin. A matrix containing a drug or a drug reservoir supplies the drug through the skin over a period of time such as several hours or days. Likewise, blood monitoring can be performed through the skin and into the patch. However, skin includes a layer known as the stratum corneum that is chiefly responsible for the barrier properties of skin to prevent transdermal flux of drugs or other molecules into the body and of analytes out of the body. The stratum corneum has a thickness of about 10 to about 40 microns and is continuously renewed by shedding of corneum cells during desquamination and the formation of new corneum cells by a keratinization process. For some drugs, such as opiates, the stratum corneum can impede significant flux, and so it is desirable to overcome this barrier to enable a wider array of topical and transdermal delivery systems.
It is generally desirable to enhance transdermal drug delivery and blood monitoring, and in this regard there are several known methods for increasing the permeability of skin to drugs. Among these is a methodology known as “microporation” or “poration,” which refers to the formation of a hole or crevice (defined herein as a “micropore”) in a biological membrane, such as skin or mucous membrane, of a patient. The micropore lessens the barrier properties of the skin to the passage of drugs into the patient for a therapeutic treatment, or of biological fluids out of the patient for analysis. The micropore can range from about 1 to about 1000 microns in diameter and typically extends into the skin sufficiently so as to reduce the barrier properties of the stratum corneum without adversely affecting the underlying tissues. Typically, multiple micropores are created in a single application of this methodology. See, for example, U.S. Pat. Nos. 5,885,211 and 7,141,034 (the '034 patent) for a description of various thermal and electrical microporation techniques and devices.
In order to create micropores, energy is applied to the skin surface. In the '034 patent, that energy is provided either by a hand-held external device or from a self-contained unit that combines a transdermal delivery device with an energy source. The devices proposed by the '034 patent are multi-part assemblies, which appear to be cumbersome and awkward to use. It would be preferable to have a light-weight, flexible transdermal device that is electrically chargeable and fully disposable as compared to the assemblies described in the '034 patent. Alternatively, there are disposable transdermal patches with chemical reservoirs that can be mixed together to create an exothermal reaction, which might be made suitable for creating a micropore; however, the chemicals required and their associated reactions introduce substantial complexities into the manufacture of the transdermal device.
Further, effective poration of tissue requires good contact between the porator and skin, and mechanisms that assist in this regard such as devices that apply negative pressure to draw the porator closer to skin again are cumbersome.
Accordingly, there remains a need for improved methods and devices for the transdermal delivery of agents such as drugs, and for the monitoring of analytes such as blood components. The present invention concerns transdermal delivery devices of this nature.